KRAS Copy Number Gain in Cell-Free DNA Analysis-Based Liquid Biopsy of Plasma and Bile in Patients with Various Pancreatic Neoplasms

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Abstract
Cell-free DNA (cfDNA) analysis-based liquid biopsy is a rapidly emerging diagnostic and prognostic tool in pancreatic ductal adenocarcinoma (PDAC). KRAS point mutations are the main biomarkers used for the detection of tumor cfDNA. However, there is another less studied yet frequent genetic alteration in this gene, namely copy number gain (CNG). The aim of this study was to evaluate the diagnostic and prognostic potential of KRAS CNG analysis in plasma and bile of patients with PDAC using ddPCR. This study included healthy volunteers (n = 69), patients with PDAC (n = 94), and other pancreatic neoplasms (OPN) (n = 17). The sensitivity and specificity of KRAS CNG compared to the control group were 16% and 100% (AUC-ROC—0.580), and compared to the OPN group, 16% and 94% (AUC-ROC—0.554), respectively. Addition of KRAS point mutations to the analysis increased the sensitivity to 65% (AUC-ROC—0.824 and 0.801, respectively). Bile exhibited an equal KRAS CNG detection rate compared to plasma (20% vs. 16%). KRAS CNG was not associated with clinical parameters, except prognosis. The probability of survival was worse in patients with KRAS CNG (HR—3.54; 95% CI: 1.55–8.12; p = 0.001). KRAS CNG in cfDNA might be a promising biomarker for both diagnostic and prognostic purposes in PDAC.
Funding Information
  • Lomonosov Moscow State University

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